Recurrent cardiac arrhythmia is a serious health concern affecting more than 4 million Americans and accounts for 20% of all deaths related to heart disease. In advanced cases when drug therapy is ineffective, arrhythmias are often treated with resynchronization or ablation therapy. Intracardiac ablation procedures to correct drug-resistant arrhythmias depend on accurate maps of the cardiac activation wave. Despite global success of interventional cardiac surgery for treatment of arrhythmias, electrophysiological (EP) mapping of the heart has significant limitations; for example, the complex and expensive procedure is prone to image registration errors, not effective for identifying transient arrhythmias, and has relatively poor spatial resolution (5-10 mm). To overcome several limitations and dramatically improve EP mapping procedures, we propose a novel modality for real-time imaging of current flow and biopotentials in the heart. As such, this project would develop Ultrasound Current Source Density Imaging (UCSDI) to greatly enhance and facilitate EP mapping of the heart. UCSDI is based on an acoustoelectric (AE) interaction between local pressure and resistivity to remotely detect current flow in tissue. As we have demonstrated in a variety of preparations, ultrasound passing through tissue generates a voltage modulation (the AE signal) close to the ultrasound frequency and proportional to the local current density. UCSDI would facilitate image guidance during ablation treatment of arrhythmias and other cardiac disorders through 1) direct 3D imaging of current flow and cardiac potentials in the heart; 2) enhanced spatial resolution determined primarily by the size of the ultrasound focus; and 3) automatic co-registration with pulse echo ultrasound (echocardiograms) for overlaying current flow maps with cardiac anatomy and motion. The following specific aims are central for testing this hypothesis. SA.1. Enhance UCSDI system hardware and software SA.2. Determine fundamental limits of sensitivity and resolution SA.3. Interface UCSDI system with commercial intracardiac catheter This project would dramatically improve our existing UCSDI system, identify limits of sensitivity and spatial resolution for EP mapping of the cardiac activation wave using UCSDI, and demonstrate feasibility using a clinical intracardiac catheter. A successful outcome would lead to a 5-year renewal focusing on in vivo studies and translation to the operating room. PUBLIC HEALTH RELEVANCE: This proposal will develop 3D ultrasound current source density imaging (UCSDI), a new modality based on an interaction between ultrasound and conductive tissue, to map electrical activity in the heart. An optimized imaging system would greatly facilitate and enhance electrophysiological mapping of the heart for treatment of arrhythmias.